Phase 1/2a Study of BMS-986523 Monotherapy and Combination Therapy in Participants with KRAS-Altered Advanced Solid Malignancies

The primary objective is to evaluate the safety, tolerability, dose response, and optimal dosing schedule of BMS-986523 as a monotherapy or in combination with pembrolizumab, cetuximab, or gemcitabine and nab-paclitaxel in patients with advanced solid tumors harboring KRAS alterations. Secondary objectives include:

• Assessment of preliminary efficacy of the investigated regimens.
• Evaluation of pharmacokinetics and pharmacodynamics following oral administration of BMS-986523, both alone and in combination with the specified agents.

This study involves 236 patients with advanced solid tumor malignancies. The study population includes both males and females within the age ranges of 18-44 and 45-64 years. Participants must have a histologically confirmed diagnosis of a locally advanced, unresectable, or metastatic malignancy featuring a known KRAS alteration, such as a mutation or amplification. The cohort is further categorized by specific tumor types, including non-small cell lung cancer, colorectal cancer, and pancreatic adenocarcinoma. Eligible individuals are those who have previously received, are ineligible for, or have declined specific standard of care treatments depending on the assigned study arm.

This Phase 1/2a, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BMS-986523. The investigation focuses on participants with advanced solid malignancies harboring KRAS alterations. The study will assess the administration of BMS-986523 as a monotherapy or in combination with anti-cancer agents, specifically pembrolizumab, cetuximab, or gemcitabine plus nab-paclitaxel. The primary endpoint involves monitoring the frequency of adverse events, including dose-limiting toxicity. Secondary endpoints include the overall response rate determined by RECIST v1.1 and pharmacokinetic parameters such as Cmax, Tmax, and AUC.

The experimental treatment consists of BMS-986523, which is administered in the form of a film-coated tablet. This substance is intended for oral use as a monotherapy or in combination with other agents in participants with advanced solid malignancies characterized by KRAS alterations.

Non-experimental treatments used in the study include pembrolizumab, cetuximab, or a combination of gemcitabine and nab-paclitaxel. These agents are evaluated in conjunction with the investigational product to assess safety, tolerability, pharmacokinetics, and pharmacodynamics.

The assessment of preliminary efficacy for BMS-986523 in participants with advanced solid malignancies featuring KRAS alterations is conducted through specific secondary endpoints. The overall response rate and the duration of response will be evaluated according to RECIST v1.1 criteria as determined by investigator assessment.